Anaes · Applied cardiovascular & respiratory physiology

Context-sensitive half-time

Also known as CSHT · Context-sensitive half time · Recovery from infusion · Drug accumulation · Remifentanil CSHT · Ester metabolism

The context-sensitive half-time (CSHT) is the time for the plasma drug concentration to fall by 50 percent after stopping an infusion of a given duration, and it is the clinically relevant measure of recovery — far more useful than the terminal half-life for drugs given by infusion. The framework rests on five exam-critical ideas: the CSHT is NOT the same as the terminal elimination half-life, because during prolonged infusion the drug accumulates in the peripheral compartments (muscle, fat), and when the infusion stops the drug redistributes BACK from the periphery into the central compartment, slowing the decline in plasma concentration; for lipophilic drugs with a large Vd (fentanyl, thiopental), the CSHT increases dramatically with infusion duration — fentanyl CSHT rises from about 30 minutes after a 1-hour infusion to about 5 hours after 8 hours; for drugs with organ-independent ester metabolism (remifentanil), the CSHT is constant at about 3 to 5 minutes regardless of infusion duration — no accumulation occurs; the CSHT determines how quickly a patient will recover after stopping an infusion, and therefore which drugs are suitable for long cases (remifentanil, remimazolam) versus short cases only (fentanyl boluses are fine, but a fentanyl infusion is a poor choice for a case needing rapid emergence); and the CSHT is the pharmacokinetic rationale for the modern balanced anaesthetic technique — using a rapidly titratable, non-accumulating opioid (remifentanil) alongside a volatile or propofol for depth. Built on the remimazolam review (Dong 2025), the remifentanil postoperative pain study (Nagasaka 2014), the ultra-short-acting opioids review (Davis 2005), the paracetamol co-administration PK study (Raffa 2018), the opioids-in-organ-failure review (Hohne 2004), and the dexmedetomidine PK/TCI review (Tsai 2026).